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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal human bronchial epithelial cells were infected with SV40 virus or an adenovirus 12-SV40 hybrid virus, or transfected via strontium phosphate coprecipitation with plasmids containing the SV40 early region genes. Colonies of morphologically altered cells were isolated and cultured; these cells had extended culture lifespans compared to normal human bronchial epithelial cells. All cultures eventually underwent senescence, with the exception of one which appears to have unlimited proliferative potential. Colonies arising after viral infection were screened for virus production by cocultivation with Vero cells; only viral nonproducer cultures were analyzed further. The cells retained electron microscopic features of epithelial cells, and keratin and SV40 T-antigen were detected by indirect immunofluorescence. All of the cultures were aneuploid with karyotypic abnormalities characteristic of SV40-transformed cells. No tumors formed after s.c. injection of the cells in nude mice. These cells should be useful for studies of multistage bronchial epithelial carcinogenesis.
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PMID:Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. 245 Jun 41

Most human ovarian cancers are thought to arise in the ovarian surface epithelium (OSE). The precise role of OSE in carcinogenesis has not been defined because no appropriate animal models for the study of this tissue exist and culture of human OSE has been limited to primary outgrowths. In this report, we describe conditions for serial cultivation of normal human OSE. Premenopausal ovarian tissue was obtained at surgery. OSE growth was compared in media MCDB 202, 199 and Waymouth's 752/1 (WM) supplemented with 5, 15, or 25% fetal bovine serum (FBS), with/without 20 ng/ml epidermal growth factor (EGF) and 0.4 micrograms/ml hydrocortisone (HC). The rate and extent of OSE outgrowths from explants in primary culture were greatest in either WM or 199/202 (1:1), supplemented with 15% FBS/EGF/HC. In early passage cultures, cell proliferation was most rapid and extensive in 199/202 with 15% FBS, EGF, and HC. In this medium, OSE cells were subcultured up to 10 times and underwent 20-25 population doublings over 5 weeks. The population doubling time during rapid growth was approximately 48 h. Seeding efficiencies of up to 53% and cloning efficiencies of up to 13% were obtained. Early passage OSE cells reversibly modulated from a slow growing, epithelial, intensely keratin-positive form in 199/202 medium lacking EGF/HC, to a rapidly proliferating, elongate, less keratin-positive form in medium with EGF/HC. OSE cells grown in WM/5-15% FBS were epithelial and near-stationary. Thus, culture conditions have been defined for ovarian carcinogen assays requiring either proliferating or stationary cell populations, and for further studies of the role of OSE in ovarian biology.
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PMID:Serial propagation of human ovarian surface epithelium in tissue culture. 245 Aug 77

Monospecific antikeratin antisera and specific complementary DNA probes were used to analyze expression of keratin genes in newborn mouse skin and skin papillomas and carcinomas by indirect immunofluorescence, immunoblotting, and in situ hybridization. Tumors were induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Type I epidermal keratin K14 protein (Mr 55,000) is found in all living layers of the newborn skin but is most abundant in the lower strata. K1 (Mr 67,000) and K10 (Mr 59,000) proteins are predominantly suprabasal and K1 is processed in the stratum corneum. Transcripts for K14 were confined largely to the basal cell layer by in situ hybridization. Transcripts for K1 and K10 were highly expressed in suprabasal cells including the granular cell layer. In benign tumors, distribution of K14 protein is similar to that in newborn skin, while the abundance of K1 and K10 appears to be somewhat reduced although the tissue distribution remains suprabasal. Transcription of K14 is aberrant in benign tumors and transcripts persist throughout much of the suprabasal cell layers. Transcripts of K1 and K10 are normally distributed in papillomas but grain density is less intense than in newborn epidermis. Keratin expression in carcinomas is highly disturbed. K14 protein and transcripts are highly expressed in all strata in carcinomas while protein and transcripts for K1 and K10 are essentially absent. These results suggest that papilloma cells fail to respond to or generate signals to regulate K14 expression in the differentiating suprabasal cell layers and may not fully express their suprabasal cell keratins. Carcinomas fail to express suprabasal cell keratins and this is regulated at the transcriptional level. The loss of suprabasal keratin expression may provide a marker for malignant conversion in the mouse skin carcinogenesis model.
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PMID:Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis. 245 88

Morphological observations suggest that rate tracheal epithelial (RTE) cells undergo squamous differentiation when maintained in cell culture. The purpose of the studies presented here was to examine and define differentiation of cultured RTE cells with the help of markers previously shown to be specific for squamous differentiation. Furthermore, we wanted to determine whether neoplastic transformation of these cells causes significant disruption of their differentiation program. Our experiments showed that squamous differentiation occurs in normal primary RTE cell cultures. Epidermal transglutaminase (transglutaminase type I) activity increased approximately 20-fold in RTE cultures as a function of time. Cholesterol sulfate, another marker of squamous differentiation, increased only modestly with time. A significant number of cells formed cross-linked envelopes in cultures growth-arrested at a cell density of approximately 250 cells/mm2. However, no significant changes in keratin expression were detected. Neoplastically transformed RTE cells which exhibit a greatly increased growth capacity expressed the same three markers of squamous differentiation as normal RTE cells. However, transglutaminase type I activity was relatively low. The cross-linked envelope formation was independent of cell density in the transformed cells. Like in normal RTE cultures, cholesterol sulfate accumulation only increased moderately with increasing cell density. The keratin pattern of transformed RTE cell lines was identical to that of normal primary RTE cells. A well-differentiated squamous cell carcinoma derived from one of the neoplastic cell lines expressed in vivo keratin markers typical of keratinization (56 kd acidic keratin and 65-67 kd basic keratins). We draw the following conclusions. (i) The biochemical studies confirm that normal RTE cells undergo squamous differentiation. The pathway of terminal squamous differentiation is cell density dependent. (ii) In transformed RTE cells, growth as well as differentiation are less subject to regulation by cell density than in normal cells. (iii) Transformed RTE cells are differentiation competent; the main abnormality appears to be that in transformed cell populations proliferation and differentiation occur concomitantly.
Carcinogenesis 1989 Apr
PMID:Squamous differentiation in normal and transformed rat tracheal epithelial cells. 246 58

The pattern of keratin expression in hamster cheek pouch epithelium during 15-wk of DMBA-induced carcinogenesis was studied. The sequential changes in cytokeratins of premalignant and malignant tissues and comparative investigation of normal epithelial tissues were examined during a weekly sequential DMBA-induced chemical carcinogenesis. Keratin polypeptides of normal pouch epithelium appear in a molecular weight range of 43-67 kd and 5-6 proteins can be identified. The disappearance of high molecular weight keratin (61-67 kd) was observed from the 6-wk DMBA-treated premalignant group to the 15-wk DMBA-treated malignant group. An additional keratin polypeptide was noted initially on the 11th-wk-DMBA-treated group and remained to the 15th-wk-DMBA treated group.
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PMID:Cytokeratins in hamster cheek pouch epithelium during DMBA-induced carcinogenesis. 247 18

Spindle cell carcinomas were identified using polyacrylamide gel electrophoresis and immunoblotting of proteins extracted from paraffin-embedded tissue sections. Immunohistochemistry using rabbit monospecific antisera against the mouse 55 kd keratin polypeptide also identified these tumors. A group of 53 SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) yielded, after one year, four spindle cell carcinomas (0.07/mouse), whereas another group of 31 mice treated with a three-stage carcinogenesis protocol (initiation with DMBA and promotion for 10 weeks with TPA followed by 10 weeks of benzoyl peroxide) gave rise to six spindle cell carcinomas (0.19/mouse). The number of keratin-positive tumor cells and the intensity of the immunostain varied markedly, but all tumors expressed the 55 kd polypeptide. Although other carcinogens, mainly UV radiation, have been able to induce spindle cell tumors, the present data indicate that chemical carcinogenesis protocols are able to induce the formation of this highly malignant variant of skin carcinoma.
Carcinogenesis 1989 Nov
PMID:Multistage chemical carcinogenesis protocols produce spindle cell carcinomas of the mouse skin. 247 10

Rat liver T51B cells were maintained in the presence of low concentrations of Ni(II) derived from alpha Ni3S2 for 3-15 months in culture in order to monitor cytokeratin, differentiation, and transformation patterns. Nickel exposures caused irreversible, heritable juxtanuclear aggregates of cytokeratin CK55, which increased in size and complexity with prolonged nickel exposure, eventually resembling Mallory bodies and expressing glutamyltransferase. Altered cytokeratin expression was accompanied by induction of differentiation, with markers of both bile ductular cells and hepatocytes, such as induction of cytokeratin polypeptides CK39 and CK49, cell morphology, and cytokeratin filament network changes; whereas control cultures similarly maintained for long periods in culture remained unchanged. Altered cytokeratin expression was also accompanied by acquisition of transformation markers--loss of density dependence, progression toward calcium independence, and (benign) growth in nude mice. Observed cytokeratin aberrations may be a factor in nickel carcinogenesis, in view of the known affinity of the metal for cellular structural proteins, especially keratin, which play a role in maintenance of cell behavior.
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PMID:Altered cytokeratin expression and differentiation induction during neoplastic transformation of cultured rat liver cells by nickel subsulfide. 248 Aug 38

Expression of four oncogenes and two keratin genes was determined in rat tracheal epithelial cell lines derived from tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Cell lines were grouped into four stages of neoplastic progression based on phenotypic markers in order to correlate oncogene expression with stage of malignancy. Northern analysis of RNA revealed a significantly enhanced expression of the c-myc oncogene in the most tumorigenic or tumor-derived cell lines, whereas preneoplastic cells expressed approximately five-fold less transcript. Southern analysis of tracheal cell DNA did not demonstrate amplification of the c-myc gene in any of the positive cell lines. In contrast to c-myc, other oncogenes such as ras and fos were expressed in all cell lines, as well as in control cell cultures, to a similar extent. Patterns of differentiation were examined in these epithelial cell lines by determining the expression of two distinct keratin genes, KA-1 and KB-2. Both malignant and preneoplastic cells expressed the KB-2 gene at variably high levels, whereas the expression of the KA-1 keratin was barely detectable in any of the cell lines. The stage-specific expression of the c-myc oncogene in these tracheal cell lines suggests a correlation between the regulation of certain oncogenes and neoplastic progression in this model of respiratory carcinogenesis.
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PMID:Oncogene expression in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. 248 55

The study of gamma-glutamyl transpeptidase (GGT) activity in transformed tissues has conventionally involved the killing of an animal or excision of the lesion, preventing longitudinal study. Oral exfoliative cytology allows longitudinal examination; however, it has been shown to be an unreliable criterion of malignancy. GGT activity has been demonstrated histochemically to involve the full thickness of the epithelium, including the keratin layer during carcinogenesis of hamster buccal pouch epithelium. This study correlates the GGT-stained foci in tissue sections and the proportion of GGT-positive cells in a superficial smear during a 13-week regime of tri-weekly topical application of 7,12-dimethylbenz[a]-anthracene (DMBA) in mineral oil. GGT-positive cells were detected in smears 3 weeks after application of the carcinogen, coincident with GGT-positive foci in tissue sections involving the keratin layer. The proportion of GGT-positive cells in each experimental period increased during the first 7 weeks of the experiment and plateaued thereafter. The number of GGT-positive foci in tissue sections in each experimental period also increased during the experiment. GGT activity was not detected in either smears or tissue sections of untreated or mineral oil treated mucosa. The correlation between the proportion of GGT-positive cells in smears and GGT-positive foci in tissue sections suggest the possibility of studying the GGT activity in an experimentally induced lesion without its elimination. Furthermore, oral exfoliative cytology using GGT staining may be useful in detecting precancerous lesions clinically.
Carcinogenesis 1989 May
PMID:Gamma-glutamyl transpeptidase activity in superficial exfoliated cells during hamster buccal pouch carcinogenesis. 256 72

As compared with the adult state, neonatal mouse skin (strain NMRI) has a hyperplastic appearance which gradually changes into the mature type between postnatal day 3 and 10. Concomitantly, the late fetal and neonatal keratin polypeptide pattern is replaced by the mature pattern. As long as the adult type of epidermal differentiation is not sufficiently developed (i.e., prior to postnatal day 5), topical application of the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes neither morphological alterations nor a measurable induction of cellular proliferation and ornithine decarboxylase activity. TPA application at day 7 evokes, however, (i) a hyperplastic reaction followed by a massive 'psoriasis-like' hyperkeratosis, (ii) an increase of ornithine decarboxylase activity and (iii) a restoration of the neonatal keratin polypeptide pattern. Multistage tumorigenesis experiments carried out with prenatally initiated mice show that during the early period of development (prior to postnatal day 5) mouse skin is also resistant to the effects of TPA as a stage I tumor promoter. Since both the hyperplastic response and the sensitivity to tumor promotion develops in a strictly parallel manner, reactions involved in the induction of epidermal hyperplasia are assumed to provide an important condition of stage I skin tumor promotion.
Carcinogenesis 1985 Feb
PMID:Development of phorbol ester responsiveness in neonatal mouse epidermis: correlation between hyperplastic response and sensitivity to first-stage tumor promotion. 257 99


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